256457-56-4

Upstream product

• 76144-87-1 (S)-(1,1'-binaphthalene)-2,2'-diylbis(diphenylphosphine) 
• 76144-87-1 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl 
• 76189-55-4 (R)-(+)-2,2'-bis(diphenylphosphino)-1,1'-binaphthalene 
• 76144-87-1 (R)-2,2'-bis(diphenylphosphanyl)-1,1'-binaphthyl 
• 83864-14-6 nickel dichloride 

Downstream Products

• 1594113-05-9 cis-[(S)-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene](2-methylphenyl)nickel(II) chloride 

Relevant academic research and scientific papers

Direct, Enantioselective, and Nickel(II) Catalyzed Reactions of N-Azidoacetyl Thioimides with Trimethyl Orthoformate: A New Combined Methodology for the Rapid Synthesis of Lacosamide and Derivatives

A direct and highly enantioselective reaction of N-azidoacetyl-1,3-thiazolidine-2-thione with trimethyl orthoformate catalyzed by Tol-BINAPNiCl2 in the presence of TESOTf and 2,6-lutidine is reported. The heterocyclic scaffold can be easily removed by addition of a wide array of amines to give the corresponding enantiomerically pure 2-azido-3,3-dimethoxypropanamides in high yields. Appropriate manipulation of the N-benzyl amide derivative provides an efficient access to the antiepileptic agent lacosamide through a new enantioselective C?C bond-forming process. DFT computational studies uncover clues for the understanding of the remarkable stereocontrol of the addition of a nickel(II) enolate to a putative oxocarbenium intermediate from trimethyl orthoformate.

Nickel-catalyzed kumada cross-coupling reactions of benzylic sulfonamides

Herein, we report a Kumada cross-coupling reaction of benzylic sulfonamides. The scope of the transformation includes acyclic and cyclic sulfonamide precursors that cleanly produce highly substituted acyclic fragments. Preliminary data are consistent with a stereospecific mechanism that allows for a diastereoselective reaction.

Stereospecific nickel-catalyzed cross-coupling reactions of benzylic ethers with isotopically-labeled grignard reagents

In this manuscript we highlight the potential of stereospecific nickel-catalyzed cross-coupling reactions for applications in the pharmaceutical industry. Using an inexpensive and sustainable nickel catalyst, we report a gram-scale Kumada cross-coupling reaction. Reactions are highly stereospecific and proceed with inversion at the benzylic position. We also expand the scope of our reaction to incorporate isotopically labeled substituents.

A broadly applicable strategy for entry into homogeneous nickel(0) catalysts from air-stable nickel(II) complexes

A series of air-stable nickel complexes of the form L2Ni(aryl) X (L = monodentate phosphine, X = Cl, Br) and LNi(aryl)X (L = bis-phosphine) have been synthesized and are presented as a library of precatalysts suitable for a wide variety of nickel-catalyzed transformations. These complexes are easily synthesized from low-cost NiCl2·6H2O or NiBr 2·3H2O and the desired ligand followed by addition of 1 equiv of Grignard reagent. A selection of these complexes were characterized by single-crystal X-ray diffraction, and an analysis of their structural features is provided. A case study of their use as precatalysts for the nickel-catalyzed carbonyl-ene reaction is presented, showing superior reactivity in comparison to reactions using Ni(cod)2. Furthermore, as the precatalysts are all stable to air, no glovebox or inert-atmosphere techniques are required to make use of these complexes for nickel-catalyzed reactions.

Controlling first-row catalysts: Amination of aryl and heteroaryl chlorides and bromides with primary aliphatic amines catalyzed by a BINAP-ligated single-component Ni(0) complex

First-row metal complexes often undergo undesirable one-electron redox processes during two-electron steps of catalytic cycles. We report the amination of aryl chlorides and bromides with primary aliphatic amines catalyzed by a well-defined, single-component nickel precursor (BINAP)Ni(η2-NC- Ph) (BINAP = 2,2′-bis(biphenylphosphino)-1,1′-binaphthalene) that minimizes the formation of Ni(I) species and (BINAP)2Ni. The scope of the reaction encompasses electronically varied aryl chlorides and nitrogen-containing heteroaryl chlorides, including pyridine, quinoline, and isoquinoline derivatives. Mechanistic studies support the catalytic cycle involving a Ni(0)/Ni(II) couple for this nickel-catalyzed amination and are inconsistent with a Ni(I) halide intermediate. Monitoring the reaction mixture by 31P NMR spectroscopy identified (BINAP)Ni(η2-NC-Ph) as the resting state of the catalyst in the amination of both aryl chlorides and bromides. Kinetic studies showed that the amination of aryl chlorides and bromides is first order in both catalyst and aryl halide and zero order in base and amine. The reaction of a representative aryl chloride is inverse first order in PhCN, but the reaction of a representative aryl bromide is zero order in PhCN. This difference in the order of the reaction in PhCN indicates that the aryl chloride reacts with (BINAP)Ni(0), formed by dissociation PhCN from (BINAP)Ni(η2-NC-Ph), but the aryl bromide directly reacts with (BINAP)Ni(η2-NC-Ph). The overall kinetic behavior is consistent with turnover-limiting oxidative addition of the aryl halide to Ni(0). Several pathways for catalyst decomposition were identified, such as the formation of the catalytically inactive bis(amine)-ligated arylnickel(II) chloride, (BINAP)2Ni(0), and the Ni(I) species [(BINAP)Ni(μ-Cl)] 2. By using a well-defined nickel complex as catalyst, the formation of (BINAP)2Ni(0) is avoided and the formation of the Ni(I) species [(BINAP)Ni(μ-Cl)]2 is minimized.

Process design and scale-up of the synthesis of 2,2′:5′,2′-terthienyl

The objective of this study was the design of a scaleable process for the synthesis of 3-4 mol of α-terthienyl from 2,5-dibromothiophene and thienylmagnesium bromide in a 10-L stirred tank reactor. In THF the Grignard reagent, thienylmagnesium bromide, was readily formed from 2-bromothiophene and magnesium. To avoid crystallization the maximal concentration was limited to 1.4 M. Furthermore, the novel combination of THF and NiCl2[bis(diphenylphosphino)benzene] allows for fast double coupling of the Grignard reagent with 2,5-dibromothiophene. The concentration of catalyst could be limited to 0.5 mol % based on the amount of 2,5-dibromothiophene. An adapted workup procedure was developed, in which n-octane was used to separate the magnesium salts from the desired product. The reaction was performed in a (semi)batch-wise operated reactor. A global model for the coupling step proved to predict the results at 0.1-, 1-, and 10-L scales very accurately. The heat of reaction evolved in the coupling step was valorized and could be handled easily. Mixing of the feed stream and the reactor content proved to be another important factor in the scaling-up of the α-terthienyl synthesis.